Unlike HPV(−)HNSCC, which is mostly associated with smoking and exhibits ubiquitous loss of TP53 function,42 HPV oncoprotein activation of PI3K–AKT–mTOR1 signalling pathway is the main driver of genomic alterations in HPV(+)OPSCC, including PIK3CA(58%), FGFR3(24%), PTEN(22%) and CYLD(16%), as observed in our study.3 Here, PIK3CA is linked to head and neck squamous cell carcinoma.